The proposed research would investigate in depth a series of initial observations made over the last three years on the toxicity and pharmacokinetics of chlordecone (Kepone R) in humans and experimental animals. These initial observations suggest that chlordecone exhibits unusual properties in its distribution, hepatic storage, biliary excretion, nonbiliary excretion, and comparative metabolism among various species. Using a wide variety of experimental models including isolated plasma lipoprotein subfractions, liver homogenates, hepatocyte cultures, intact mammals, and man, we will study in greater depth the following questions: (1) the chronic clinical manifestations (if any) of chlordecone toxicity in humans; (2) the binding of chlordecone to plasma lipoproteins; (3) mechanism of hepatic uptake and storage of chlordecone; (4) identification of chlordecone metabolites and elucidation of the enzymatic basis for inter-species differences in comparative metabolism of chlordecone; (5) the determinants of biliary secretion of chlordecone; (6) the mechanism and control of nonbiliary excretion of chlordecone. This fundamental information of the interaction of chlordecone with biological systems will serve as a basis for further investigation of the role of orally administered binding agents as therapy for human poisoning with organochlorine chemicals. Where appropriate, comparisons of pharmacokinetic parameters of chlordecone will be made with other organochlorine substances including Chlordane, Mirex, Heptachlor, and polychlorinated biphenyls. It is anticipated that the results of this research will provide badly needed information regarding an important environmental toxin, and serve as a model for investigating other environmental substances potentially hazardous to human health.